Nucleolar RNA helicase 2
Also known as: DDX21
Function
RNA helicase that acts as a sensor of the transcriptional status of both RNA polymerase (Pol) I and II: promotes ribosomal RNA (rRNA) processing and transcription from polymerase II (Pol II). Binds various RNAs, such as rRNAs, snoRNAs, 7SK and, at lower extent, mRNAs. In the nucleolus, localizes to rDNA locus, where it directly binds rRNAs and snoRNAs, and promotes rRNA transcription, processing and modification. Required for rRNA 2'-O-methylation, possibly by promoting the recruitment of late-acting snoRNAs SNORD56 and SNORD58 with pre-ribosomal complexes. In the nucleoplasm, binds 7SK RNA and is recruited to the promoters of Pol II-transcribed genes: acts by facilitating the release of P-TEFb from inhibitory 7SK snRNP in a manner that is dependent on its helicase activity, thereby promoting transcription of its target genes. Functions as a cofactor for JUN-activated transcription: required for phosphorylation of JUN at 'Ser-77'. Can unwind double-stranded RNA (helicase) and can fold or introduce a secondary structure to a single-stranded RNA (foldase). Together with SIRT7, required to prevent R-loop-associated DNA damage and transcription-associated genomic instability: deacetylation by SIRT7 activates the helicase activity, thereby overcoming R-loop-mediated stalling of RNA polymerases. Involved in rRNA processing. May bind to specific miRNA hairpins. Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1 (By similarity).
Classification
- Family (Pfam)
- PF26142 DD_DDX21-DDX50, PF00270 DEAD, PF08152 GUCT, PF00271 Helicase_C
- InterPro
- DD_DDX21-DDX50, DEAD/DEAH_box_helicase_dom, DEAD_box_RNA_helicase, GUCT, Helicase_ATP-bd, Helicase_C-like, P-loop_NTPase, RBD_domain_sf
- Functional cluster
- DEAD-Box RNA Helicases & Biogenesis Factors
Experimental structures · PDB · 5
A predicted model is available from AlphaFold.
Gene Ontology · 31
- GO:0005694 chromosome
- GO:0005829 cytosol
- GO:0016020 membrane
- GO:0005739 mitochondrion
- GO:0005730 nucleolus
- GO:0005654 nucleoplasm
- GO:0097322 7SK snRNA binding
- GO:0005524 ATP binding
- GO:0016887 ATP hydrolysis activity
- GO:0003725 double-stranded RNA binding
- GO:0042802 identical protein binding
- GO:0035198 miRNA binding
- GO:0003729 mRNA binding
- GO:0003723 RNA binding
- GO:0003724 RNA helicase activity
- GO:0140870 RNA polymerase inhibitor activity
- GO:0019843 rRNA binding
- GO:0030515 snoRNA binding
- GO:0006338 chromatin remodeling
- GO:0051607 defense response to virus
- GO:0045087 innate immune response
- GO:0016479 negative regulation of transcription by RNA polymerase I
- GO:0001649 osteoblast differentiation
- GO:0043123 positive regulation of canonical NF-kappaB signal transduction
- GO:0002735 positive regulation of myeloid dendritic cell cytokine production
- GO:0045943 positive regulation of transcription by RNA polymerase I
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0045945 positive regulation of transcription by RNA polymerase III
- GO:0062176 R-loop processing
- GO:0006364 rRNA processing
- GO:0006366 transcription by RNA polymerase II
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Nucleolar RNA helicase 2 0.94
- Nucleolar RNA helicase 2 0.92
- Nucleolar RNA helicase 2-B 0.85
- Nucleolar RNA helicase 2-A 0.85
- ATP-dependent RNA helicase DDX50 0.84
- ATP-dependent RNA helicase DDX50 0.83
- DEAD-box ATP-dependent RNA helicase 7 0.79
- DEAD-box ATP-dependent RNA helicase 7 0.76
- DEAD-box ATP-dependent RNA helicase 5 0.74
- DEAD-box ATP-dependent RNA helicase 7 0.74
- DEAD-box ATP-dependent RNA helicase 27 0.73
- Probable ATP-dependent RNA helicase DDX52 0.72
Co-cited proteins · studied together in the literature
- Glucose-induced degradation protein 4 homolog 1 shared papers
- ATP-dependent RNA helicase DDX50 2 shared papers
- WD repeat-containing protein 46 1 shared papers
- Probable rRNA-processing protein EBP2 1 shared papers
- NAD-dependent protein deacetylase sirtuin-7 1 shared papers
- Importin subunit alpha-4 1 shared papers
- Myb-binding protein 1A 1 shared papers
- Regulator of chromosome condensation 1 shared papers
- 28S rRNA (cytosine(4447)-C(5))-methyltransferase 1 shared papers
- Nucleolin 2 shared papers
- Ribosomal RNA processing protein 1 homolog A 1 shared papers
- Zinc finger CCCH domain-containing protein 7A 1 shared papers
Literature · 37 cited papers
- A chemical probe to modulate human GID4 Pro/N-degron interactions. Nat. Chem. Biol. · 2024
- Dominant KPNA3 Mutations Cause Infantile-Onset Hereditary Spastic Paraplegia. Ann. Neurol. · 2021
- SIRT7 and the DEAD-box helicase DDX21 cooperate to resolve genomic R loops and safeguard genome stability. Genes Dev. · 2017
- A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis. Mol. Cell · 2017
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- The association of late-acting snoRNPs with human pre-ribosomal complexes requires the RNA helicase DDX21. Nucleic Acids Res. · 2015
- RNA helicase DDX21 coordinates transcription and ribosomal RNA processing. Nature · 2015
- Elevated DDX21 regulates c-Jun activity and rRNA processing in human breast cancers. Breast Cancer Res. · 2014
- Mapping of SUMO sites and analysis of SUMOylation changes induced by external stimuli. Proc. Natl. Acad. Sci. U.S.A. · 2014
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Nucleolar scaffold protein, WDR46, determines the granular compartmental localization of nucleolin and DDX21. Genes Cells · 2013
- GANP regulates recruitment of AID to immunoglobulin variable regions by modulating transcription and nucleosome occupancy. Nat. Commun. · 2013
- … and 25 more in the literature graph